SUMMARY OF WORK Recent findings support the view that the role of high sodium intake in the development of hypertension can be mediated by chronic behavioral stress. One way in which behaviral stress can influence sodium regulation is via conditioned suppression of breathing, which increases pCO2, changes acid-base balance, and increases plasma volume, perhaps via increased renal sodium-hydrogen exchange. Previous studies in our laboratory showed that humans who characteristically maintain end tidal CO2 near the upper end of the normal range have blood pressure that is more sensitive to the effects of high dietary sodium intake than those who characteristically maintain lower end tidal CO2. That high end tidal CO2 is characteristic of relative plasma volume expansion is indicated by observations that subjects with high end tidal CO2 have higher levels of endogenous digitalis like factors (EDLF) than control subjects, even before sodium loading.Over the past year, a study with 314 healthy men and women participating in the Baltimore Longitudinal Study on Aging has been completed. Resting PetCO2 and blood pressure of each participant was recorded prospectively, while slopes of the rate of change in blood pressure over 22 ? 1 yrs were calculated retrospectively for 74 older, long-term participants. Multiple regressions were performed to determine the extent to which PetCO2 was an independent predictor of current blood pressures and blood pressure increases over years. Resting PetCO2 of men, which decreased with age, was found to be an independent predictor of the rate of increase of systolic blood pressure over years, but not of current blood pressure level. PetCO2 of women, which remained stable over the life span, was an independent predictor of both systolic blood pressure increase and current level. The mechanisms by which pCO2 participates in long-term blood pressure regulation, and the origins of these gender differences remain to be clarified. Studies are proposed to investigate the effects of high sodium diet on postmenopausal women, who are at increased risk for hypertension following loss of estrogen, and of the effects of estrogen replacement therapy on that sodium sensitivity. - aging, blood pressure, carbon dioxide, hypertension, pCO2, respiration - Human Subjects